Effects of mechanical forces on signal transduction and gene expression in endothelial cells.
Fluid shear stress and circumferential stretch play important roles in maintaining the homeostasis of the blood vessel, and they can also be pathophysiological factors in cardiovascular diseases such as atherosclerosis and hypertension. The uses of flow channels and stretch devices as in vitro models have helped to elucidate the mechanisms of signal transduction and gene expression in cultured endothelial cells in response to shear stress, which is a function of blood flow and vascular geometry, or mechanical strain, which is a function of transmural pressure and the mechanical properties and geometry of the vessel. Shear stress has been found to increase the activities of a number of kinases to modulate the phosphorylation of many signaling proteins in endothelial cells, eg, the proteins in focal adhesion sites and the proteins in the mitogen-activated protein kinase pathways. Downstream to such signaling cascades, multiple transcription factors such as AP-1, NF-kappaB, Sp-1, and Egr-1 are activated. The actions of these transcription factors on the corresponding cis-elements result in the induction of genes encoding for vasoactivators, adhesion molecules, monocyte chemoattractants, and growth factors in endothelial cells, thus modulating vascular structure and function. Some of the effects of mechanical strain on endothelial cells are similar to those by shear stress, eg, the signaling pathways and the genes activated, but there are differences, eg, the time course of the responses. Studies on the effects of mechanical forces on signal transduction and gene expression provide insights into the molecular mechanisms by which hemodynamic factors regulate vascular physiology, and pathophysiology.
Chien
S
S
Department of Bioengineering and Institute for Biomedical Engineering, University of California, San Diego, La Jolla 92093-0412, USA. schien@bioeng.ucsd.edu
Li
S
S
Shyy
Y J
YJ
D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical